8e4t: Difference between revisions
No edit summary |
No edit summary |
||
(2 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
The | ==Crystal structure of the kinase domain of RTKC8 from the choanoflagellate Monosiga brevicollis== | ||
<StructureSection load='8e4t' size='340' side='right'caption='[[8e4t]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8e4t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Monosiga_brevicollis Monosiga brevicollis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E4T FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8e4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e4t OCA], [https://pdbe.org/8e4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e4t RCSB], [https://www.ebi.ac.uk/pdbsum/8e4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e4t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A9VBW0_MONBE A9VBW0_MONBE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Genomic analysis of the unicellular choanoflagellate, Monosiga brevicollis (MB), revealed the remarkable presence of cell signaling and adhesion protein domains that are characteristically associated with metazoans. Strikingly, receptor tyrosine kinases, one of the most critical elements of signal transduction and communication in metazoans, are present in choanoflagellates. We determined the crystal structure at 1.95 A resolution of the kinase domain of the M. brevicollis receptor tyrosine kinase C8 (RTKC8, a member of the choanoflagellate receptor tyrosine kinase C family) bound to the kinase inhibitor staurospaurine. The chonanoflagellate kinase domain is closely related in sequence to mammalian tyrosine kinases (~ 40% sequence identity to the human Ephrin kinase domain EphA3) and, as expected, has the canonical protein kinase fold. The kinase is structurally most similar to human Ephrin (EphA5), even though the extracellular sensor domain is completely different from that of Ephrin. The RTKC8 kinase domain is in an active conformation, with two staurosporine molecules bound to the kinase, one at the active site and another at the peptide-substrate binding site. To our knowledge this is the first example of staurospaurine binding in the Aurora A activation segment (AAS). We also show that the RTKC8 kinase domain can phosphorylate tyrosine residues in peptides from its C-terminal tail segment which is presumably the mechanism by which it transmits the extracellular stimuli to alter cellular function. | |||
Crystal structure of the kinase domain of a receptor tyrosine kinase from a choanoflagellate, Monosiga brevicollis.,Bajaj T, Kuriyan J, Gee CL PLoS One. 2023 Jun 13;18(6):e0276413. doi: 10.1371/journal.pone.0276413. , eCollection 2023. PMID:37310965<ref>PMID:37310965</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8e4t" style="background-color:#fffaf0;"></div> | ||
[[Category: Gee | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Monosiga brevicollis]] | |||
[[Category: Bajaj T]] | |||
[[Category: Gee CL]] | |||
[[Category: Kuriyan J]] |
Latest revision as of 13:17, 25 October 2023
Crystal structure of the kinase domain of RTKC8 from the choanoflagellate Monosiga brevicollisCrystal structure of the kinase domain of RTKC8 from the choanoflagellate Monosiga brevicollis
Structural highlights
FunctionPublication Abstract from PubMedGenomic analysis of the unicellular choanoflagellate, Monosiga brevicollis (MB), revealed the remarkable presence of cell signaling and adhesion protein domains that are characteristically associated with metazoans. Strikingly, receptor tyrosine kinases, one of the most critical elements of signal transduction and communication in metazoans, are present in choanoflagellates. We determined the crystal structure at 1.95 A resolution of the kinase domain of the M. brevicollis receptor tyrosine kinase C8 (RTKC8, a member of the choanoflagellate receptor tyrosine kinase C family) bound to the kinase inhibitor staurospaurine. The chonanoflagellate kinase domain is closely related in sequence to mammalian tyrosine kinases (~ 40% sequence identity to the human Ephrin kinase domain EphA3) and, as expected, has the canonical protein kinase fold. The kinase is structurally most similar to human Ephrin (EphA5), even though the extracellular sensor domain is completely different from that of Ephrin. The RTKC8 kinase domain is in an active conformation, with two staurosporine molecules bound to the kinase, one at the active site and another at the peptide-substrate binding site. To our knowledge this is the first example of staurospaurine binding in the Aurora A activation segment (AAS). We also show that the RTKC8 kinase domain can phosphorylate tyrosine residues in peptides from its C-terminal tail segment which is presumably the mechanism by which it transmits the extracellular stimuli to alter cellular function. Crystal structure of the kinase domain of a receptor tyrosine kinase from a choanoflagellate, Monosiga brevicollis.,Bajaj T, Kuriyan J, Gee CL PLoS One. 2023 Jun 13;18(6):e0276413. doi: 10.1371/journal.pone.0276413. , eCollection 2023. PMID:37310965[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
|